Loss of EGFR Mutation Expression Induced by NF1 Mutation in Non-Small Cell Lung Cancer: Non-Canonical Pathway of Tyrosine Kinase Inhibitors’ Resistance

Abstract

Non-small cell lung carcinoma (NSCLC) is considered the first cause of cancer-related death worldwide and many therapies have been developed against the presence of actionable mutations. For example, targeting the EGFR mutation has changed the overall prognosis in NSCLC. However, resistance to treatment has emerged and many canonical mechanisms have already been described. NF1 mutation causes partial or total loss of function of neurofibromin, which activates several intracellular pathways (MAPK / ERK, PI3K / AKT, TGF -β / Smad), producing cellular proliferation, migration, apoptosis resistance and genetic instability, leading to loss of EGFR expression. Herein, we describe a case of a novel activation of a non-canonical pathway that led to treatment resistance by NF1 mutation.